Since the amount of a sample extracted from a living body for experiments in molecular biology and those involving molecular biology is conventionally limited, a great challenge is to detect a target in a small amount of the sample and obtain a large quantity of data from it by reacting the sample with high efficiency. An efficiency of reaction on a plane as exemplified by a DNA chip (microarray) is limited, and therefore, there is an effort afoot to carry out a reaction on a cubic body, specifically on spherical beads.
When beads are used, acquirement of position information on the beads becomes a key. As a currently widely used method, there is a method in which information on beads themselves and a sample is obtained by attaching tags to the bead themselves. This method is applied using beads having a relatively small diameter, e.g. about several micrometers. When the size of beads is small, the number of biomolecules immobilized on the beads is limited. Accordingly, when a large amount of a biomolecule, e.g. A, is contained in a sample, a plurality of beads A′ corresponding to A are used for the reaction. Thus, the amount of the biomolecule A in the sample is measured by the number of the bead A′.
There is another method in which the property of biomolecules on beads is determined by preparing a specific reagent after arraying beads. Since there is no need to be strict about the diameter of the beads in this method and it may range from about several micrometers to one hundred micrometers, the amount of a biomolecule B in a sample, for example, may be determined either by measuring the number of its corresponding bead B′ as described above or by using only a single piece of the bead B′ and measuring a fluorescence intensity of the bead B′, thus allowing selection of either method depending on the circumstances.
However, these methods inevitably require identification of biomolecules immobilized on beads for which repetitive work is necessary several times using specific reagents, and therefore take time. Further, since these methods do not take a form that becomes generally and widely available and basically suppliers conduct its work, users cannot customize the reaction condition and the like.
Recently, a method different from these methods in which beads are put in a groove or tube slightly larger than the bead size and a reaction is carried out therein has emerged (JP-A No. 346842/2000). Since the reaction is carried out by feeding a reaction solution and the like into the groove or tube, the reaction time becomes shorter than that needed for a microarray method owing to occurrence of turbulent flow. Further, information on the beads is in hand because of predetermination of the bead array from the beginning, thereby saving in time and in labor compared with the above two methods. There are additional advantages in this method that preparation of a bead array can be customized, beads can be sealed for transportation, and so on. The fact that beads can be sealed for transportation means that the bead array can be manufactured as a product, that is, its general and widespread use can be aimed at a relatively low cost. Furthermore, users can also customize the bead array, providing an advantage of adaptability to changing circumstances.
It is also possible for the users to change reaction conditions each time in this method, and more accurate experimental results can be obtained under the conditions suitable for each sample.